In ruminants, ingested feed first passes into the rumen, where it is pre-digested or degraded by fermentation. During this period of fermentation the ingested feed may be regurgitated to the mouth where it is salivated and masticated. After a period of fermentation regulated by natural processes and variables depending on the animal and the feedstuff, absorption of digested nutrients starts and continues in the subsequent sections of the digestive tract by the ruminant animal. This process is described in detail by D. C. Church, "Digestive Physiology and Nutrition of Ruminants", Vol. 1, Oregon State University Press.
The rumen, the largest of the four stomach compartments of ruminants, serves as an important location for metabolic breakdown of ingested foodstuffs through the action of microorganisms which are present therein. Ingested food is typically retained in the rumen for from about 6 to 30 hours during which time it is subject to metabolic breakdown by the rumen microorganisms. Much ingested protein material is broken down in the rumen to soluble peptides and amino acids and utilized by the rumen microorganisms. When the rumen contents pass into the abomasum and intestine, the microbial mass is digested, thus providing protein to the ruminant. Thus, the natural nutritional balance of the ruminant animal is primarily a function of the microbial composition and population.
In preparing nutrients and medicaments intended for administration to ruminants, it is important to protect the active ingredients against the environmental conditions of the rumen, i.e., microbial degradation and the effects of a pH of about 5.5, so the active substance will be saved until it reaches the particular location where absorption takes place. It is well known that the rate of meat, wool and/or milk production can be increased if sources of growth limiting essential amino acids, and/or medicaments, are protected from alteration by microorganisms residing in the rumen and become available for direct absorption by the animal later in the gastrointestinal tract.
Materials which protect the core against degradation by the rumen contents should be resistant to attack by the rumen fluid which contains enzymes or microorganisms but must make the active ingredient available rapidly in the more acidic fluid of the abomasum at a pH within the normal physiological range of about 2 to about 3.5. To more easily coat or encapsulate active ingredients in protective materials, the protective materials should be soluble in certain organic solvents for coating purposes.
Because proteins are subject to breakdown in the rumen, it has been suggested that protein-containing nutrients fed to ruminants be treated so as to permit passage without microbial breakdown through the rumen to the abomasum. Suggested procedures have included coating the protein material, for example, with fats and vegetable oils; heat treating of the protein material; reacting the protein material with various compounds such as formaldehyde, acetylenic esters, polymerized unsaturated carboxylic acid or anhydrides and phosphonitrilic halides, etc.
It is well known that all proteins found in animal and plant life are chemical compounds containing different combinations of over 02 amino acids, the number and arrangement of such acids being fixed in any particular protein. Twelve of these amino acids can be synthesized in nutritionally adequate amounts from other substances by biochemical processing normally present in most animals, but the remaining 10 essential amino acids are not synthesized in sufficient quantities and must be ingested by the animal. Since the proportions of the constituent amino acids in a particular protein cannot be varied, the essential amino acid least in supply limits the amounts of that protein which can be produced by the animal. Consequently, for any given diet, there will be a particular essential amino acid which limits the production of protein incorporating that essential amino acid unless, of course, two or more such amino acids are equally limiting.
The application of the above principles leads to the formulation of diets for nonruminant animals which provide the optimum proportion of amino acids and have enabled significant increases in protein production to be achieved. In the ruminant, dietary proteins and amino acids are, to a variable extent, broken down to ammonia and various organic compounds by microbial fermentation in the first two compartments of the stomach (the rumen and reticulum). The bacteria and protozoa in these organs utilize these metabolites for their own growth and multiplication and the microbial protein so formed passes on to the abomasum, the compartment of the stomach corresponding to the stomach of nonruminants, where it is partially digested. The process is completed in the small intestine and the amino acids are absorbed.
It is likewise well-known that medicaments are more effective when they are protected from the environment of the rumen. See, for example, U.S. Pat. Nos. 3,041,243 and 3,697,640.
The need and the value of post-ruminal delivery of nutrients and pharamaceuticals by means of supplementing rumen-stable preparations in feed is discussed in a paper entitled, "Controlled-Release Additives for Ruminants: Cellullose-Based Coating Composition for Rumen-Stable Nutrients", by Wu, et al, in a book, Controlled Release of Pesticides and Pharmaceuticals, edited by D. H. Lewis, Plenum Press, New York, N.Y., 1981, p. 319.
The following patents by Dannelly, et al, teach the art of formulating rumen-stable coatings for a variety of nutrients and medicaments: U.S. Pat. Nos. 4,117,801; 4,177,255; 4,181,708; 4,181,709; 4,181,710; and 4,196,187.
U.S. Pat. No. 4,181,708 specifically teaches the ternary composition of a rumen-stable coating which comprises a polymeric material such as a copolymer of 2-methyl-5-vinylpyridine and styrene [copoly(2M5VP/ST)] which is resistant to mildly acidic environment of the rumen, and a hydrophobic substance of from about 5 to 50% of the polymer weight, and a flake material of from about 10 to 200% of the polymer weight dispersed throughout the continuous matrix. U.S. Pat. No. 4,181,709 specifically teaches the quaternary composition of a rumen-stable coating which comprises a polymeric material such as copoly(2M5VP/ST), a hydrophobic material of from about 2 to about 40% of the polymer weight, and a reactive fatty acid of from about 5 to about 40% of the polymer weight. U.S. Pat. No. 4,181,710 specifically teaches a binary composition of rumen-stable coating comprised of a polymeric matrix and a hydrophobic material being present in an amount between 5-50% of the polymer weight.
U.S. Pat. No. 4,177,255 specifically teaches a composition for a rumen stable coating which comprises a polymeric matrix which is resistant to acid and a substance dispersed therein which is leachable from the matrix in the environment of the abomasum but not the rumen.
Other patents of interest are as follows:
U.S. Pat. No. 3,619,200 relates to chemically modifying pellets and/or using a surface coating therefor. Various polymers are disclosed in this patent including copolymers of vinylpyridine and styrene. Canadian Pat. No. 911,649 discloses treatment of proeteinaceous materials with substances which are capable of reacting with proteins to form a polymeric proteinaceous complex on the surface of the material or by treating the proteinaceous material with a polymer or copolymer of a basic vinyl or acrylic monomer. This patent also discloses the use of copolymers and terpolymers derived from essentially a basic substituted acrylate or methacrylate monomer and at least one ethylenically unsaturated compound as rumen stable coatings. U.S. Pat. No. 3,880,990 and British Pat. No. 1,346,739 relate to an orally administratable ruminant composition where in a medicinal substance is encapsulated or embedded in a normally solid, physiologically acceptable basic polymer. The compositions are produced by dispersing a medicinal substance in a first solvent and adding thereto a second solvent which is miscible with the first solvent but in which the polymer and medicinal substance are substantially insoluble. U.S. Pat. No. 3, 041,243 relates to coatings for oral medicaments. These coatings are water-insoluble but acid-soluble film-forming polymers. An example mentioned in this patent is 2-methyl-5-vinylpyridine copolymerized with vinyl acetate acrylonitrile, methyl acrylate or styrene.
U.S. Pat. No. 3,697,640 relates to materials such as medicaments and nutrients for ruminants which are coated with nitrogen-containing cellulosic materials such as, for example, cellulose propionate morpholino butyrate. U.S. Pat. No. 3,988,480 relates to a proteinaceous feedstuff for ruminants which has been treated with acetic acid to render it rumen stable.
U.S. Pat. No. 3,383,283 relates to coating pharmaceutical pellets with a plurality of charges of fatty acid as a melt or in solution. The fatty acid may then be dusted with a fine inert powder such as talc.
U.S. Pat. No. 3,275,518 relates to a tablet coating composition comprising a film-forning resin or plastic and a hard water-soluble or water-dispersible substance. Stearic acid is mentioned as an optional water-insoluble wax which may be included as an additive. Additional materials such as dyes, pigments, water-insoluble waxes, plasticizing agents, etc., may also be added to the coating.
U.S. Pat. No. 3,623,997 relates to a method of sealing polymeric material walls of minute capsules by treating the capsules with a waxy material.
U.S. Pat. No. 3,073,748 relates to tablets coated with a solution of an amphoteric film-forming polymer. The polymer is described as one selected from the group consisting of copolymer of (a) vinylpyridines with (b) a lower aliphatic, a,B-unsaturated monocarboxylic acid of 3 to 4 carbon atoms and copolymers of (a), (b) and a neutral comonomer selected from the group consisting of methyl acrylate, acrylonitrile, vinyl acetate, methyl methacrylate and styrene.
British Pat. No. 1,217,365 and Canadian counterpart No. 851,128 relate to a particulate feed additive composition for ruminants wherein each particle comprises one or more amino acids totally encased in a continuous film of protective material which is transportable through the rumen without substantial degradation therein but which releases the active substance posterior to the omasum. Suggested as protective materials are fatty acid triglycerides such a hydrogenated vegetable and animal fast, waxes such as rice-brand wax, and resin wax blends which are emulsified and/or dissolved in the intestinal tract.
Also of interest is U.S. Pat. No. 4,060,598 which relates to coated tablets prepared by applying to a core of active material a coating composition made up of a film forming aqueous synthetic resin dispersion and a water or alkaline soluble material.
This invention describes binary coating compositions comprised of a polymer and at least one inorganic substance which are suitable for rumen-stable preparation of nutrients and medicaments such a methionine, glucose, and lysine.